1. Field of the Invention
This invention relates to stable solid or semi-solid water-in-oil emulsions that are usable as bioadherent, ingestible systems. The systems are designed to coat and adhere to the oral cavity, epithelial and mucosal membranes of the esophagus and gastrointestinal (GI) tract for extended periods of time. The purpose of the coating is to protect the mouth tissue and the membranes of the pharynx and the esophagus, while promoting healing and to enable release of active drug in a delayed release rate. Confectionery and chewing gum compositions containing the emulsions are also described.
2. Description of the Prior Art
Oral pharmaceutical formulations are administered to patients in many forms, such as liquid solutions, emulsions, or suspensions, as well as in solid forms such as capsules or tablets. Preparations administered in tablet or capsule form are usually intended to be swallowed whole. It is of significant advantage to both the patient and clinician that medication be formulated so that it may be administered in a minimum number of daily doses from which the drug is uniformly released over a desired extended period of time. Various techniques have been developed for the purpose of including a pharmaceutical preparation comprising a drug-containing particle with a coating layer and a pharmaceutical preparation comprising a continuous matrix with a drug dispersed therein, such as embedded into a rigid lattice of resinous material in order to control the release of drugs. Representative U.S. Patents covering this technology include the following patents:
U.S. Pat. No. 5,059,426 to Cherukuri et al. discloses a process for preparing a delivery system comprised of a zinc core material coated with a first hydrophilic coating comprising a hydrocolloid material and a second hydrophobic coating selected from the group consisting of fats, waxes and mixtures thereof. The delivery system masks the bitter flavor characteristic of zinc compounds.
U.S. Pat. No. 4,597,970 to Sharma et al. discloses a delivery system capable of effecting a controlled release of core material comprising: (a) at least one natural or artificial sweet material and (b) a hydrophobic matrix consisting essentially of (i) lecithin; and (ii) an edible material having a melting point in the range of about 25.degree. C. to about 100.degree. C. selected from the group consisting of (a) fatty acids having an iodine value of about 1 to about 10, (b) natural waxes, (c) synthetic waxes and (d) mixtures thereof; and (iii) at least one glyceride.
U.S. Pat. No. 4,695,467 to Uemura et al. relates to a sustained release tablet which comprises easily disintegratable granules containing (a) a drug, (b) a disintegrating agent selected from the group consisting of starch derivatives, gums, cellulose derivatives and ion-exchange resins, and (c) a water-soluble polymer selected from the group consisting of cellulose derivatives, synthetic water soluble polymers and polysaccharides, the surfaces of which granules are treated with a wax selected from the group consisting of plant or animal wax, hydrogenated oils and paraffin.
Other forms for delivering pharmaceutical agents include emulsions and suspensions. Although a need for water-in-oil emulsions having a high water or aqueous phase content has long existed for use in pharmaceutical preparations, such as night creams or barrier creams and lotions, it has been difficult to provide such emulsion where the aqueous phase exceeds 45% to 55% on a weight by weight basis. Although many benefits are to be derived from providing a high water content in a water-in-oil emulsion system for cosmetic applications in particular, formulators have not heretofore been able to add more than about 50% water to the emulsion without seriously affecting the shelf life stability of the preparation. It is to be appreciated in this respect that because of the time delay that occurs between formulation of a product and commercial sale, it is undesirable to employ an emulsion which will break in a short period of time, particularly when exposed to temperature extremes that are encountered during transportation and warehouse storage. Although stability under normal climatic conditions is an asset, at the very minimum the emulsion system should be able to withstand temperatures on the order of 43.degree. C. (110.degree. F.) for at least six months without breaking.
Water-in-oil- emulsions are used in barrier preparations or pore-occluding products to provide a thin oleaginous-layer over the areas of the user's skin to which the composition is applied. Increasing the amount of hydrophilic inner phase in the emulsion decreases the oily feel of the material without deleteriously effecting the overall utility of the formulation. Such formulations have greater customer appeal because the higher hydrophilic content enhances the evaporative and thereby cooling effect of the cream or lotion upon application. Products formulated from these emulsion systems are described in U.S. Pat. No. 4,385,049 to Robert C. Cuca.
The use of water-in-oil emulsions as a liquid or semi-liquid system for oral use have not been successful. U.S. Pat. No. 2,948,686 to Gianladis describes water-in-oil emulsions but the patentee was not able to incorporate more than about 52% water in the emulsion system.
The present invention overcomes these deficiencies by preparing an orally useable and stable solid or semi-solid emulsion or suspension having an internal hydrophilic phase with a multifunctional hydrophobic external phase containing at least three separate components, an emulsifier, a glyceride ester and a wax material. Such systems enable the inventive formulation, when taken orally to coat and protect the oral cavity, and membranes of the esophagus and pharynx while enabling an active drug to be released from the formulation in a delayed rate of release.